Design, Synthesis,\nand Biological Activity Evaluation\nof Eco-Friendly Rosin-Diamide-Based Fungicides as Potential Succinate\nDehydrogenase Inhibitors for Sustainable Crop Protection

To develop novel succinate dehydrogenase\n(SDH) inhibitors\nfor sustainable\ncrop protection, a series of dehydroabietyl-diamide-based fungicides\n(a total of 21) were designed. In vitro fungicidal activity measurement\nshowed that compound <b>3u</b> exhibited excellent fungicidal\nactivity against Valsa mali (half-maximal\neffective concentration, EC<sub>50</sub> = 0.195 μg/mL), surpassing\nthat of the positive control carbendazim (EC<sub>50</sub> = 1.35 μg/mL).\nThe in vivo fungicidal activity assessment suggested that <b>3u</b> exhibited a protective effect on apple branches (69.7–48.1%)\nand apples (94.6–56.6%). Furthermore, biosafety evaluation\nindicated that <b>3u</b> was significantly environmentally friendly\ntoward zebrafish. Subsequently, morphology, physiology, and molecular\ndocking were investigated to elucidate the mode of action of <b>3u</b> against V. mali. Results\ndemonstrated a strong binding between <b>3u</b> and SDH, resulting\nin decreased SDH activity (half-maximal inhibitory concentration,\nIC<sub>50</sub> = 11.7 μg/mL). Moreover, <b>3u</b> disrupted\nthe mycelial cell membrane and accelerated electrolyte leakage, ultimately\nresulting in the death of V. mali.\nThese findings suggest that <b>3u</b> could serve as a potent\nSDH inhibitor for sustainable crop protection.